(1) Field of the Invention
This invention relates to a device and a method for determining concentration of ionic liquid components contained in test samples, using electrically contacted substrates such as ion-selective electrodes. The device particularly concerns means for mounting electrodes so as to minimize errors in the readings obtained, and preferably is used in potentiometrically measuring ion activity in drops of biological fluids. Such measurements are used to measure the health of patients from which the fluids are taken, and can be ascertained either by a direct or a differential mode of measurement.
(2) State of the Prior Art
The prior art is replete with a great variety of electrode types and structures for the measurement of various ions in solution. Typically, devices for obtaining such measurements include a reference electrode and an ion-selective electrode (hereafter termed ISE) which incorporates a reference half-cell, generally comprising a solution of known ion activity. When simultaneously immersed into the same body of solution to be analyzed, the reference electrode and the ISE constitute an electrochemical cell, across the electrodes of which a potential develops. This potential is proportional to the logarithm of the activity of the ions in the solution to which the ISE is sensitive. The foregoing relationship between the potential and the activity of the selected ion in solution is described by the well-known Nernst equation. An electromagnetic device, usually either a direct-reading circuit or a null-balance potentiomeric circuit, is employed for measuring the potential between the electrodes.
Prior electrodes include barrel types, which have required large amounts of test solution into which they are immersed. U.S. Pat. Nos. 3,598,713; 3,502,560; 3,575,834 to Hoole issued Apr. 20, 1971; 3,753,887 to Kedem et al. issued Aug. 21, 1973 and U.S. Pat. No. 3,855,100 provide detailed descriptions of electrodes of this type. Such electrodes are not suitable for measuring drop-size amounts. Micro-amounts, if usable, would have a distinct advantage over large quantities, as the amounts of sample taken from the patient can be considerably reduced.
Yet another disadvantage of large, bulky electrodes such as the barrel type in their expense. Such devices do not lend themselves to the economy of mass production. A much desired improvement is an electrode whose mass-producible construction reduces its cost such that the electrode can be used once and disposed of, eliminating cleaning between tests and potential contamination.
Some miniaturization has been achieved by electrodes other than ion-selective electrodes and their supporting equipment. One example is the probe shown in British patent specification No. 1,318,815, wherein two electrodes are mounted spaced apart with a semipermeable matrix overlying the electrodes. However, there is no indication that these electrodes are to be used with drop-sized quantities of liquid or are disposable. Other miniaturized test elements have been developed, such as electrophoretic cells, wherein two electrodes are connected by a strip prewetted or precoated with an electrolyte to provide electrolytic connection to the electrodes when a drop of the test sample, such as blood serum, is applied to the strip. An example is shown in U.S. Pat. No. 3,826,734. However, the electrodes and mounting frame of such test elements are not designed for automated handling.
A solid state type of ion-selective electrode of greatly simplified construction is shown in U.S. Pat. No. 3,856,649 issued to Genshaw et al. on Dec. 24, 1974. Although the disclosure suggests that such ISE's could be constructed in sheet form, there is no teaching as to the manner in which the electrodes are useful or can be used in automated handling equipment. Specific problems of such automation are not dealt with.
Thin-layer chromatographic sheets, described hereinafter in connection with one embodiment of the invention, are of course, conventional and comprise a support coated with a layer such as silica gel mixed with a binder and a thickener to promote spreading of solvents. However, the test samples applied to such sheets are confined to a single spot or line, and separate test samples are deliberately segregated from each other.
U.S. Pat. No. 3,855,100 is an example of one type of salt bridge used in pH measurements.